The objectives of this research program are to continue our studies of the control aspects of purine biosynthesis in liver and cultured human fibroblasts, and to elucidate the ways in which defective regulation of these processes leads to gout. These objectives are necessary for an understanding of the way the mammal regulates the production of the relatively insoluble metabolite uric acid. This will be approached by studying individual components of the purine synthesizing and interconverting machinery in liver of rats under dietary conditions known to have markedly different rates of purine biosynthesis. These investigations will also be supplemented by studies on cultured fibroblasts from normal as well as patients with clinical gout.